LC-2 - CAS 2502156-03-6

LC-2 is a PROTAC® Degrader of KRAS G12C containing a von-Hippel-Lindau (VHL) E3 ligase ligand and the covalently bound inhibitor MRTX849 with a DC50 value between 0.25 and 0.76 μM, which can induce rapid and sustained degradation of KRAS G12C.

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Molecular Formula
Molecular Weight


    • Specification
      • Purity
        Soluble in DMSO
        White Solid
        Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)
        Room temperature in continental US; may vary elsewhere.
        IUPAC Name
    • Properties
      • Density
        1.297±0.06 g/cm3
        InChI Key
        Canonical SMILES
        Pub Chem ID
    • Reference Reading
      • 1. Targeted degradation of oncogenic KRASG12C by VHL-recruiting PROTACs.
        Bond, M.J., Chu, L., Nalawansha, D.A., Li, K. and Crews, C.M., 2020. ACS central science, 6(8), pp.1367-1375.
        KRAS is mutated in ~20% of human cancers and is one of the most sought-after targets for pharmacological modulation, despite having historically been considered "undruggable." The discovery of potent covalent inhibitors of the KRASG12C mutant in recent years has sparked a new wave of interest in small molecules targeting KRAS. While these inhibitors have shown promise in the clinic, we wanted to explore PROTAC-mediated degradation as a complementary strategy to modulate mutant KRAS. Herein, we report the development of LC-2, the first PROTAC capable of degrading endogenous KRASG12C. LC-2 covalently binds KRASG12C with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRASG12C degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRASG12C cell lines. LC-2 demonstrates that PROTAC-mediated degradation is a viable option for attenuating oncogenic KRAS levels and downstream signaling in cancer cells.
    • Preparing Stock Solutions
      • ConcentrationVolumeMass1 mg5 mg10 mg
        1 mM0.88 mL4.41 mL8.83 mL
        5 mM0.18 mL0.88 mL1.77 mL
        10 mM0.09 mL0.44 mL0.88 mL
        50 mM0.02 mL0.09 mL0.18 mL
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